{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:06:59Z","timestamp":1791227219313,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science KAKENHI","award":["22K09668"],"award-info":[{"award-number":["22K09668"]}]},{"name":"Japan Society for the Promotion of Science KAKENHI","award":["H30-Nanchitou (Nan)-Ippan-016"],"award-info":[{"award-number":["H30-Nanchitou (Nan)-Ippan-016"]}]},{"name":"Japan Society for the Promotion of Science KAKENHI","award":["SR22001"],"award-info":[{"award-number":["SR22001"]}]},{"name":"Health Labor Sciences Research","award":["22K09668"],"award-info":[{"award-number":["22K09668"]}]},{"name":"Health Labor Sciences Research","award":["H30-Nanchitou (Nan)-Ippan-016"],"award-info":[{"award-number":["H30-Nanchitou (Nan)-Ippan-016"]}]},{"name":"Health Labor Sciences Research","award":["SR22001"],"award-info":[{"award-number":["SR22001"]}]},{"name":"Society for Promotion of International Oto-Rhino-Laryngology (SPIO) Japan, SODA TOYOJI SPIO Research","award":["22K09668"],"award-info":[{"award-number":["22K09668"]}]},{"name":"Society for Promotion of International Oto-Rhino-Laryngology (SPIO) Japan, SODA TOYOJI SPIO Research","award":["H30-Nanchitou (Nan)-Ippan-016"],"award-info":[{"award-number":["H30-Nanchitou (Nan)-Ippan-016"]}]},{"name":"Society for Promotion of International Oto-Rhino-Laryngology (SPIO) Japan, SODA TOYOJI SPIO Research","award":["SR22001"],"award-info":[{"award-number":["SR22001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The bitter taste receptors (T2Rs) expressed in human sinonasal mucosae are known to elicit innate immune responses involving the release of nitric oxide (NO). We investigated the expression and distribution of two T2Rs, T2R14 and T2R38, in patients with chronic rhinosinusitis (CRS) and correlated the results with fractional exhaled NO (FeNO) levels and genotype of the T2R38 gene (TAS2R38). Using the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) phenotypic criteria, we identified CRS patients as either eosinophilic (ECRS, n = 36) or non-eosinophilic (non-ECRS, n = 56) patients and compared these groups with 51 non-CRS subjects. Mucosal specimens from the ethmoid sinus, nasal polyps, and inferior turbinate were collected from all subjects, together with blood samples, for RT-PCR analysis, immunostaining, and single nucleotide polymorphism (SNP) typing. We observed significant downregulation of T2R38 mRNA levels in the ethmoid mucosa of non-ECRS patients and in the nasal polyps of ECRS patients. No significant differences in T2R14 or T2R38 mRNA levels were found among the inferior turbinate mucosae of the three groups. Positive T2R38 immunoreactivity was localized mainly in epithelial ciliated cells, whereas secretary goblet cells generally showed lack of staining. The patients in the non-ECRS group showed significantly lower oral and nasal FeNO levels compared with the control group. There was a trend towards higher CRS prevalence in the PAV\/AVI and AVI\/AVI genotype groups as compared to the PAV\/PAV group. Our findings reveal complex but important roles of T2R38 function in ciliated cells associated with specific CRS phenotypes, suggesting the T2R38 pathway as a potential therapeutic target for promotion of endogenous defense mechanisms.<\/jats:p>","DOI":"10.3390\/ijms24054499","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T03:23:36Z","timestamp":1677468216000},"page":"4499","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Functional Alteration and Differential Expression of the Bitter Taste Receptor T2R38 in Human Paranasal Sinus in Patients with Chronic Rhinosinusitis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8531-7821","authenticated-orcid":false,"given":"Kota","family":"Takemoto","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2737-4697","authenticated-orcid":false,"given":"Luga Santo","family":"Lomude","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9853-2501","authenticated-orcid":false,"given":"Sachio","family":"Takeno","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Kawasumi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukako","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9728-1264","authenticated-orcid":false,"given":"Takao","family":"Hamamoto","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0646-0839","authenticated-orcid":false,"given":"Takashi","family":"Ishino","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9386-2990","authenticated-orcid":false,"given":"Yuki","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1016\/S0960-9822(96)00704-X","article-title":"Chemoreception: Tasting the sweet and the bitter","volume":"6","author":"Lindemann","year":"1996","journal-title":"Curr. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"D1179","DOI":"10.1093\/nar\/gky974","article-title":"BitterDB: Taste ligands and receptors database in 2019","volume":"47","author":"Nissim","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/chemse\/bjp092","article-title":"The molecular receptive ranges of human TAS2R bitter taste receptors","volume":"35","author":"Meyerhof","year":"2010","journal-title":"Chem. Senses"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jaggupilli, A., Howard, R., Aluko, R.E., and Chelikani, P. (2019). Advanced Glycation End-Products Can Activate or Block Bitter Taste Receptors. Nutrients, 11.","DOI":"10.3390\/nu11061317"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/apha.12621","article-title":"The bitter truth about bitter taste receptors: Beyond sensing bitter in the oral cavity","volume":"216","author":"Avau","year":"2016","journal-title":"Acta. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.biocel.2016.03.011","article-title":"Bitter taste receptors: Extraoral roles in pathophysiology","volume":"77","author":"Shaik","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1085\/jgp.201611637","article-title":"Extraoral bitter taste receptors in health and disease","volume":"149","author":"Lu","year":"2017","journal-title":"J. Gen. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1021\/acsinfecdis.8b00094","article-title":"Characterization of the Binding Sites for Bacterial Acyl Homoserine Lactones (AHLs) on Human Bitter Taste Receptors (T2Rs)","volume":"4","author":"Jaggupilli","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Workman, A.D., Patel, N.N., Carey, R.M., Kuan, E.C., and Cohen, N.A. (2018). The Role of Taste Receptors in Airway Innate Immune Defense. Sinusitis, 3.","DOI":"10.3390\/sinusitis3020006"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"L603","DOI":"10.1152\/ajplung.00283.2020","article-title":"First contact: The role of respiratory cilia in host-pathogen interactions in the airways","volume":"319","author":"Kuek","year":"2020","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/alr.21275","article-title":"Genetic variations in taste receptors are associated with chronic rhinosinusitis: A replication study","volume":"4","author":"Boisvert","year":"2014","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/alr.21253","article-title":"The bitter taste receptor T2R38 is an independent risk factor for chronic rhinosinusitis requiring sinus surgery","volume":"4","author":"Adappa","year":"2014","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/alr.21803","article-title":"Correlation of T2R38 taste phenotype and in vitro biofilm formation from nonpolypoid chronic rhinosinusitis patients","volume":"6","author":"Adappa","year":"2016","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"90","DOI":"10.4193\/Rhin16.181","article-title":"The impact of bitter taste receptor genetics on culturable bacteria in chronic rhinosinusitis","volume":"55","author":"Rom","year":"2017","journal-title":"Rhinology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kawasumi, T., Takeno, S., Ishikawa, C., Takahara, D., Taruya, T., Takemoto, K., Hamamoto, T., Ishino, T., and Ueda, T. (2021). The Functional Diversity of Nitric Oxide Synthase Isoforms in Human Nose and Paranasal Sinuses: Contrasting Pathophysiological Aspects in Nasal Allergy and Chronic Rhinosinusitis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147561"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1093\/chemse\/bjz042","article-title":"Expression of Bitter Taste Receptors and Solitary Chemosensory Cell Markers in the Human Sinonasal Cavity","volume":"44","author":"Chen","year":"2019","journal-title":"Chem. Senses"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8484","DOI":"10.1074\/jbc.M116.771949","article-title":"Flavones modulate respiratory epithelial innate immunity: Anti-inflammatory effects and activation of the T2R14 receptor","volume":"292","author":"Hariri","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1096\/fj.13-242594","article-title":"The bitter pill: Clinical drugs that activate the human bitter taste receptor TAS2R14","volume":"28","author":"Levit","year":"2014","journal-title":"FASEB J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kuek, L.E., McMahon, D.B., Ma, R.Z., Miller, Z.A., Jolivert, J.F., Adappa, N.D., Palmer, J.N., and Lee, R.J. (2022). Cilia Stimulatory and Antibacterial Activities of T2R Bitter Taste Receptor Agonist Diphenhydramine: Insights into Repurposing Bitter Drugs for Nasal Infections. Pharmaceuticals, 15.","DOI":"10.3390\/ph15040452"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin20.401","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.jaci.2016.06.063","article-title":"Heterogeneous inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois","volume":"139","author":"Tan","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1111\/all.12644","article-title":"Novel scoring system and algorithm for classifying chronic rhinosinusitis: The JESREC Study","volume":"70","author":"Tokunaga","year":"2015","journal-title":"Allergy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.alit.2019.07.002","article-title":"Eosinophilic chronic rhinosinusitis","volume":"68","author":"Fujieda","year":"2019","journal-title":"Allergol. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"32","DOI":"10.4193\/Rhin17.255","article-title":"The Global Allergy and Asthma European Network (GALEN rhinosinusitis cohort: A large European cross-sectional study of chronic rhinosinusitis patients with and without nasal polyps","volume":"57","author":"Khan","year":"2019","journal-title":"Rhinology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/alr.22686","article-title":"Divergent bitter and sweet taste perception intensity in chronic rhinosinusitis patients","volume":"11","author":"Lin","year":"2021","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"835151","DOI":"10.3389\/falgy.2022.835151","article-title":"Studies on Clinical Features, Mechanisms, and Management of Olfactory Dysfunction Secondary to Chronic Rhinosinusitis","volume":"3","author":"Lin","year":"2022","journal-title":"Front. Allergy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2473974X20986756","DOI":"10.1177\/2473974X20986756","article-title":"Smell and Taste Impairment in a Nationwide Sample of US Adults with Chronic Rhinosinusitis Symptoms","volume":"5","author":"Kim","year":"2021","journal-title":"OTO Open"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1002\/alr.22687","article-title":"Denatonium benzoate bitter taste perception in chronic rhinosinusitis subgroups","volume":"11","author":"Civantos","year":"2021","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e216","DOI":"10.1542\/peds.2004-1582","article-title":"Genetic and environmental determinants of bitter perception and sweet preferences","volume":"115","author":"Mennella","year":"2005","journal-title":"Pediatrics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1093\/chemse\/bjq132","article-title":"Allelic variation in TAS2R bitter receptor genes associates with variation in sensations from and ingestive behaviors toward common bitter beverages in adults","volume":"36","author":"Hayes","year":"2011","journal-title":"Chem. Senses"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1172\/JCI64240","article-title":"T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection","volume":"122","author":"Lee","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2500\/ajra.2017.31.4424","article-title":"Nitric oxide production is stimulated by bitter taste receptors ubiquitously expressed in the sinonasal cavity","volume":"31","author":"Yan","year":"2017","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/cea.12666","article-title":"A Comprehensive Review of the Nasal Microbiome in Chronic Rhinosinusitis (CRS)","volume":"46","author":"Mahdavinia","year":"2016","journal-title":"Clin. Exp. Allergy"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.jaip.2016.05.007","article-title":"Chronic Rhinosinusitis Phenotypes: An Approach to Better Medical Care for Chronic Rhinosinusitis","volume":"4","author":"Cho","year":"2016","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.jaci.2015.12.1324","article-title":"Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers","volume":"137","author":"Tomassen","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1111\/all.15074","article-title":"Endotypes of chronic rhinosinusitis: Relationships to disease phenotypes, pathogenesis, clinical findings, and treatment approaches","volume":"77","author":"Kato","year":"2022","journal-title":"Allergy"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Brzost, J., Czerwaty, K., D\u017caman, K., Ludwig, N., Piszczatowska, K., and Szczepa\u0144ski, M.J. (2022). Perspectives in Therapy of Chronic Rhinosinusitis. Diagnostics, 12.","DOI":"10.3390\/diagnostics12102301"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/chemse\/bjz019","article-title":"Mammalian Taste Cells Express Functional Olfactory Receptors","volume":"44","author":"Malik","year":"2019","journal-title":"Chem. Senses"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/alr.21149","article-title":"Solitary chemosensory cells and bitter taste receptor signaling in human sinonasal mucosa","volume":"3","author":"Barham","year":"2013","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/lary.30112","article-title":"Chronic Rhinosinusitis: T2r38 Genotyping and Nasal Cytology in Primary Ciliary Dyskinesia","volume":"133","author":"Piatt","year":"2023","journal-title":"Laryngoscope"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.alit.2016.11.001","article-title":"Japanese Guidelines for Allergic Rhinitis 2017","volume":"66","author":"Okubo","year":"2017","journal-title":"Allergol. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1369\/jhc.6A7089.2007","article-title":"Nitric Oxide-Dependent Cilia Regulatory Enzyme Localization in Bovine Bronchial Epithelial Cells","volume":"55","author":"Stout","year":"2007","journal-title":"J. Histochem. Cytochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1126\/science.1173869","article-title":"Motile cilia of human airway epithelia are chemosensory","volume":"325","author":"Shah","year":"2009","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s00005-020-00593-3","article-title":"The expression of bitter taste receptor TAS2R38 in patients with chronic rhinosinusitis","volume":"68","author":"Stachowiak","year":"2020","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/lary.26198","article-title":"The Genetics of the Bitter Taste Receptor T2R38 in Upper Airway Innate Immunity and Implications for Chronic Rhinosinusitis","volume":"127","author":"Cohen","year":"2017","journal-title":"Laryngoscope"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1002\/alr.21966","article-title":"Relative susceptibility of airway organisms to antimicrobial effects of nitric oxide","volume":"7","author":"Workman","year":"2017","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"American Thoracic Society, and European Respiratory Society (2005). ATS\/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am. J. Respir. Crit. Care Med., 171, 912\u2013930.","DOI":"10.1164\/rccm.200406-710ST"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.anl.2013.02.001","article-title":"Increased Exhaled Nitric Oxide and Its Oxidation Metabolism in Eosinophilic Chronic Rhinosinusitis","volume":"40","author":"Takeno","year":"2013","journal-title":"Auris Nasus Larynx"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1080\/02770903.2021.1897837","article-title":"Nasal Polyp Eosinophilia and FeNO May Predict Asthma Symptoms Development after Endoscopic Sinus Surgery in CRS Patients without Asthma","volume":"59","author":"Kurokawa","year":"2022","journal-title":"J. Asthma"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"59","DOI":"10.4193\/Rhin17.111","article-title":"Exhaled and Nasal Nitric Oxide in Chronic Rhinosinusitis Patients with Nasal Polyps in Primary Care","volume":"56","author":"Hakansson","year":"2018","journal-title":"Rhinology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1002\/alr.22276","article-title":"Broncho-Vaxom\u00ae (OM-85 BV) soluble components stimulate sinonasal innate immunity","volume":"9","author":"Triantafillou","year":"2019","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Carey, R.M., Adappa, N.D., Palmer, J.N., and Lee, R.J. (2021). Neuropeptide Y Reduces Nasal Epithelial T2R Bitter Taste Receptor-Stimulated Nitric Oxide Production. Nutrients, 13.","DOI":"10.3390\/nu13103392"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Biarn\u00e9s, X., Marchiori, A., Giorgetti, A., Lanzara, C., Gasparini, P., Carloni, P., Born, S., Brockhoff, A., Behrens, M., and Meyerhof, W. (2010). Insights into the binding of Phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012394"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.3945\/ajcn.113.066688","article-title":"Human bitter perception correlates with bitter receptor messenger RNA expression in taste cells","volume":"98","author":"Lipchock","year":"2013","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/alr.21666","article-title":"TAS2R38 genotype predicts surgical outcome in nonpolypoid chronic rhinosinusitis","volume":"6","author":"Adappa","year":"2016","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.1073\/pnas.0911934107","article-title":"Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals","volume":"107","author":"Tizzano","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"20587392211052948","DOI":"10.1177\/20587392211052948","article-title":"Nitric oxide synthase-2 (CCTTT)n polymorphism is associated with local gene expression and clinical manifestations in patients with chronic rhinosinusitis","volume":"20","author":"Takemoto","year":"2022","journal-title":"Eur. J. Inflamm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1177\/000348949510410s02","article-title":"Quantification for staging sinusitis. The Staging and Therapy Group","volume":"167","author":"Lund","year":"1995","journal-title":"Ann. Otol. Rhinol. Laryngol. Suppl."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"93","DOI":"10.2332\/allergolint.11-OA-0318","article-title":"Measurements of nasal fractional exhaled nitric oxide with a hand-held device in patients with allergic rhinitis: Relation to cedar pollen dispersion and laser surgery","volume":"61","author":"Takeno","year":"2012","journal-title":"Allergol. Int."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4499\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:41:34Z","timestamp":1760121694000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,24]]},"references-count":59,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24054499"],"URL":"https:\/\/doi.org\/10.3390\/ijms24054499","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,24]]}}}